Carrier system for specific artery wall gene delivery

Abstract

An artery wall binding peptide (AWBP) based on the artery wall cell-binding domain of apolipoprotein B-100 was conjugated to a cationic backbone configured for forming a complex with a nucleic acid to produce a composition that enhances gene transfer to artery wall cells. An illustrative cationic backbone is poly(ethylene glycol)-grafted-poly(L-lysine) (PEG-g-PLL). Methods of making and using the composition for gene transfer are also described.

1. A composition of matter comprising an artery wall binding peptide (SEQ ID NO:2) covalently coupled to a pharmaceutically acceptable cationic molecule, complex, or conjugate, wherein said cationic molecule, complex, or conjugate is configured for complexing with a nucleic acid. 
     
     
       2. The composition of matter of  claim 1  wherein said artery wall binding peptide (SEQ ID NO:2) is present in a molar ratio to said cationic molecule, complex, or conjugate of greater than 1:1. 
     
     
       3. The composition of matter of  claim 2  wherein said artery wall binding peptide (SEQ ID NO:2) is present in a molar ratio to said cationic molecule, complex, or conjugate of at least 2:1. 
     
     
       4. The composition of matter of  claim 1  wherein said cationic molecule, complex, or conjugate comprises a cationic polymer. 
     
     
       5. The composition of matter of  claim 4  wherein said cationic polymer comprises poly(L-lysine). 
     
     
       6. The composition of matter of  claim 4  wherein said cationic polymer comprises poly(ethylene glycol)-grafted-poly(L-lysine). 
     
     
       7. A composition of matter having the formula (AWBP) n -PEG-g-PLL, wherein AWBP is an artery wall binding peptide (SEQ ID NO: 2), n is an integer of at least 1, and PEG-g-PLL is poly(ethylene glycol)-grafted-poly(L-lysine). 
     
     
       8. The composition of matter of  claim 7  wherein n is 4. 
     
     
       9. A composition of matter comprising artery wall binding peptide (SEQ ID NO:2) covalently coupled to poly(ethylene glycol)-grafted-poly(L-lysine). 
     
     
       10. The composition of matter of  claim 9  wherein artery wall binding peptide (SEQ ID NO:2) is covalently coupled to poly(ethylene glycol)-grafted-poly(L-lysine) in a molar ratio of about 4:1. 
     
     
       11. A method of making a composition having the formula: (AWBP) n -PEG-g-PLL, wherein AWBP is an artery wall binding peptide (SEQ ID NO: 2), n is an integer of at least 1, and PEG-g-PLL is poly(ethylene glycol)-grafted-poly(L-lysine), comprising: (a) conjugating poly(ethylene glycol) to poly(L-lysine) to result in poly(ethylene glycol)-grafted-poly(L-lysine); and (b) conjugating artery wall binding peptide (SEQ ID NO: 2) to the poly(ethylene glycol)-grafted-poly(L-lysine) to result in (AWBP) n -PEG-g-PLL. 
     
     
       12. The method of  claim 11  wherein n is 4. 
     
     
       13. A method for delivering a nucleic acid to a cell in vitro bearing a receptor that binds an artery wall binding peptide (SEQ ID NO: 2) comprising: (a) mixing the nucleic acid with a composition of matter comprising an artery wall binding peptide (SEQ ID NO: 2) covalently coupled to poly(ethylene glycol)-grafted-poly(L-lysine) to result in a complex comprising a nucleic acid, a poly(ethylene glycol)-grafted-poly(L-lysine) and an artery wall binding peptide (SEQ ID NO: 2) and (b) causing the complex to contact the cell in vitro such that the receptor binds the artery wall binding peptide (SEQ ID NO: 2), thereby delivering the nucleic acid to the cell. 
     
     
       14. The method of  claim 13  wherein the artery wall binding peptide (SEQ ID NO:2) is covalently coupled to the poly(ethylene glycol)-grafted-poly(L-lysine) in a molar ratio of about 4:1.